Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
Add more filters










Publication year range
1.
ChemSusChem ; : e202400292, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38477977

ABSTRACT

A continuous flow metal-free protocol for the synthesis of sulfonyl chlorides from thiols and disulfides in the presence of nitric acid, hydrochloric acid and oxygen was developed. The influence of the reaction parameters was investigated under batch and flow conditions. Online 19F NMR was successfully implemented to investigate different reaction conditions within a single experiment. The sulfonyl chlorides were isolated (mostly in 70-81 % yield) after performing a simple aqueous washing procedure. In particular, the protocol was successfully operated for >6 hours to convert diphenyl disulfide to its corresponding sulfonyl chloride, achieving a throughput of 3.7 g h-1. The environmental impact of the protocol was assessed and compared to an existing continuous flow protocol using 1,3-dichloro-5,5-dimethylhydantoin (DCH) as reagent. The process mass intensity (PMI) for the newly-developed flow protocol (15) compared favorably to the DCH flow process (20).

2.
Chem Sci ; 14(29): 7905-7912, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37502327

ABSTRACT

Hydantoins are important scaffolds in natural products and pharmaceuticals, with only a few synthetic strategies available for their asymmetric preparation. We herein describe a single-step enantioselective synthesis of 5-monosubstituted hydantoins via condensation of glyoxals and ureas in the presence of a chiral phosphoric acid at room temperature. Products were formed in up to 99% yield and 98 : 2 e.r. Using mechanistic and kinetic studies, including time course 1H NMR monitoring, we revealed that the reaction likely proceeds via face-selective protonation of an enol-type intermediate.

3.
J Org Chem ; 88(9): 6227-6231, 2023 May 05.
Article in English | MEDLINE | ID: mdl-37014222

ABSTRACT

A challenging step in the preparation of tetrahydrocannabinol analogs is an acid-catalyzed intramolecular cyclization of the cannabidiol precursor. This step typically affords a mixture of products, which requires extensive purification to obtain any pure products. We report the development of two continuous-flow protocols for the preparation of (-)-trans-Δ9-tetrahydrocannabinol and (-)-trans-Δ8-tetrahydrocannabinol.

4.
ChemSusChem ; 16(2): e202201868, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36377674

ABSTRACT

Persulfuric acid is a well-known oxidant in various industrial-scale purification procedures. However, due to its tendency toward explosive decomposition, its usefulness in organic synthesis remained largely underexplored. Herein, a continuous in situ persulfuric acid generator was developed and applied for oxidative esterification of aldehydes under flow conditions. Sulfuric acid served as a readily available and benign precursor to form persulfuric acid in situ. By taking advantage of the continuous-flow generator concept, safety hazards were significantly reduced, whilst a robust and effective approach was ensured for direct transformations of aldehydes to valuable esters. The process proved useful for the transformation of diverse aliphatic as well as aromatic aldehydes, while its preparative capability was verified by the multigram-scale synthesis of a pharmaceutically relevant key intermediate. The present flow protocol demonstrates the safe, sustainable, and scalable application of persulfuric acid in a manner that would not be amenable to conventional batch processing.

5.
Chemistry ; 26(58): 13108-13117, 2020 Oct 15.
Article in English | MEDLINE | ID: mdl-32515835

ABSTRACT

The use of gases as reagents in organic synthesis can be very challenging, particularly at a laboratory scale. This Concept takes into account recent studies to make the case that gases can indeed be efficiently and safely formed from relatively inexpensive commercially available reagents for use in a wide range of organic transformations. In particular, we argue that the exploitation of continuous flow membrane reactors enables the effective separation of the chemistry necessary for gas formation from the chemistry for gas consumption, with these two stages often containing incompatible chemistry. The approach outlined eliminates the need to store and transport excessive amounts of potentially toxic, reactive or explosive gases. The on-demand generation, separation and reaction of a number of gases, including carbon monoxide, diazomethane, trifluoromethyl diazomethane, hydrogen cyanide, ammonia and formaldehyde, is discussed.

6.
RSC Adv ; 10(38): 22449-22453, 2020 Jun 10.
Article in English | MEDLINE | ID: mdl-35514543

ABSTRACT

This communication describes the palladium-catalyzed reductive carbonylation of aryl fluorosulfonates (ArOSO2F) using syngas as an inexpensive and sustainable source of carbon monoxide and hydrogen. The conversion of phenols to aryl fluorosulfonates can be conveniently achieved by employing the inexpensive commodity chemical sulfuryl fluoride (SO2F2) and base. The developed continuous flow formylation protocol requires relatively low loadings for palladium acetate (1.25 mol%) and ligand (2.5 mol%). Good to excellent yields of aryl aldehydes were obtained within 45 min for substrates containing electron withdrawing substituents, and 2 h for substrates containing electron donating substituents. The optimal reaction conditions were identified as 120 °C temperature and 20 bar pressure in dimethyl sulfoxide (DMSO) as solvent. DMSO was crucial in suppressing Pd black formation and enhancing reaction rate and selectivity.

7.
ChemCatChem ; 11(3): 997-1001, 2019 Feb 06.
Article in English | MEDLINE | ID: mdl-31681449

ABSTRACT

The development of a continuous-flow protocol for a palladium-catalyzed methoxycarbonylation of (hetero)aryl chlorides using carbon monoxide gas and methanol is described. (Hetero)aryl chlorides are the least expensive of the aryl halides, but are underutilized in carbonylation reactions due to their very poor reactivity. The described protocol exploits intensified conditions at elevated temperature and pressure, which are readily accessed within a continuous-flow environment, to provide moderate to excellent product yields (11 examples) in a short 16 min residence time. The continuous-flow protocol enables the safe and potentially scalable carbonylation of aryl chlorides using CO gas.

8.
Org Lett ; 21(13): 5326-5330, 2019 Jul 05.
Article in English | MEDLINE | ID: mdl-31247792

ABSTRACT

A continuous process for the on-demand generation, separation, and reaction of hydrogen cyanide (HCN) using membrane separation technology was developed. The inner tube of the reactor is manufactured from a gas-permeable, hydrophobic fluoropolymer (Teflon AF-2400) membrane. HCN is formed from aqueous reagents within the inner tube and then diffuses through the membrane into an outer tubing containing organic solvent. This technique enabled the safe handling of HCN for three different organic transformations without the need for distillation.

9.
Top Curr Chem (Cham) ; 377(2): 7, 2019 02 07.
Article in English | MEDLINE | ID: mdl-30729395

ABSTRACT

The publisher regrets that due to a conversion problem there were mistakes in this article.

10.
ChemSusChem ; 12(1): 326-337, 2019 Jan 10.
Article in English | MEDLINE | ID: mdl-30300970

ABSTRACT

A continuous-flow protocol utilizing syngas (CO and H2 ) was developed for the palladium-catalyzed reductive carbonylation of (hetero)aryl bromides to their corresponding (hetero)aryl aldehydes. The optimization of temperature, pressure, catalyst and ligand loading, and residence time resulted in process-intensified flow conditions for the transformation. In addition, a key benefit of investigating the reaction in flow is the ability to precisely control the CO-to-H2 stoichiometric ratio, which was identified as having a critical influence on yield. The protocol proceeds with low catalyst and ligand loadings: palladium acetate (1 mol % or below) and cataCXium A (3 mol % or below). A variety of (hetero)aryl bromides at a 3 mmol scale were converted to their corresponding (hetero)aryl aldehydes at 12 bar pressure (CO/H2 =1:3) and 120 °C reaction temperature within 45 min residence time to afford products mostly in good-to-excellent yields (17 examples). In particular, a successful scale-up was achieved over 415 min operation time for the reductive carbonylation of 2-bromo-6-methoxynaphthalene to synthesize 3.8 g of 6-methoxy-2-naphthaldehyde in 85 % isolated yield. Studies were conducted to understand catalyst decomposition within the reactor by using inductively coupled plasma-mass spectrometry (ICP-MS) analysis. The palladium could easily be recovered using an aqueous nitric acid wash post reaction. Mechanistic aspects and the scope of the transformation are discussed.

11.
Top Curr Chem (Cham) ; 377(1): 2, 2018 Dec 11.
Article in English | MEDLINE | ID: mdl-30536152

ABSTRACT

Molecular oxygen (O2) is the ultimate "green" oxidant for organic synthesis. There has been recent intensive research within the synthetic community to develop new selective liquid phase aerobic oxidation methodologies as a response to the necessity to reduce the environmental impact of chemical synthesis and manufacture. Green and sustainable chemical processes rely not only on effective chemistry but also on the implementation of reactor technologies that enhance reaction performance and overall safety. Continuous flow reactors have facilitated safer and more efficient utilization of O2, whilst enabling protocols to be scalable. In this article, we discuss recent advancements in the utilization of continuous processing for aerobic oxidations. The translation of aerobic oxidation from batch protocols to continuous flow processes, including process intensification (high T/p), is examined. The use of "synthetic air", typically consisting of less than 10% O2 in N2, is compared to pure O2 (100% O2) as an oxidant source in terms of process efficiency and safety. Examples of homogeneous catalysis and heterogeneous (packed bed) catalysis are provided. The application of flow photoreactors for the in situ formation of singlet oxygen (1O2) for use in organic reactions, as well as the implementation of membrane technologies, green solvents and recent reactor solutions for handling O2 are covered.


Subject(s)
Oxygen/chemistry , Oxidation-Reduction
12.
React Chem Eng ; 2(2): 103-108, 2017 Apr 01.
Article in English | MEDLINE | ID: mdl-28580177

ABSTRACT

Today, the generation of kinetic models is still seen as a resource intensive and specialised activity. We report an efficient method of generating reaction profiles from transient flows using a state-of-the-art continuous-flow platform. Experimental data for multistep aromatic nucleophilic substitution reactions are collected from an automated linear gradient flow ramp with online HPLC at the reactor outlet. Using this approach, we generated 16 profiles, at 3 different inlet concentrations and 4 temperatures, in less than 3 hours run time. The kinetic parameters, 4 rate constants and 4 activation energies were fitted with less than 4% uncertainty. We derived an expression for the error in the observed rate constants due to dispersion and showed that such error is 5% or lower. The large range of operational conditions prevented the need to isolate individual reaction steps. Our approach enables early identification of the sensitivity of product quality to parameter changes and early use of unit operation models to identify optimal process-equipment combinations in silico, greatly reducing scale up risks.

13.
ChemSusChem ; 10(1): 32-41, 2017 Jan 10.
Article in English | MEDLINE | ID: mdl-27863103

ABSTRACT

Molecular oxygen is arguably the greenest reagent available to the organic chemist. Most commonly, a diluted form of oxygen gas, consisting of less than 10 % O2 in N2 ("synthetic air"), is used in pharmaceutical and fine chemical batch manufacturing to effectively address safety concerns when handling molecular oxygen. Concentrations of O2 in N2 below 10 % are generally required to prevent the risk of combustions in the presence of flammable organic solvents ("limiting oxygen concentration"). Nonetheless, the use of pure oxygen is more efficient than using O2 diluted with N2 and can often provide enhanced reaction rates, resulting in significant improvements in product quality and process efficiency. This Concept takes into account recent studies to make the argument that, for liquid-phase aerobic oxidations, pure oxygen can indeed be handled safely on large scale by employing continuous-flow reactors, while also providing highly convincing synthetic and manufacturing benefits.


Subject(s)
Oxygen/chemistry , Pharmaceutical Preparations/chemistry , Safety , Solvents/chemistry
SELECTION OF CITATIONS
SEARCH DETAIL
...